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Oral regimen for high dose methotrexate urine alkalinization: a systematic review and meta-analysis

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Abstract

Objective

Urine alkalinization prevents nephrotoxicity in patients receiving high-dose methotrexate (HDMTX). While the standard approach involves IV sodium bicarbonate, alternative oral bicarbonate regimens are crucial in drug shortages and outpatient settings. This study aims to review the efficacy and safety of such regimens.

Methods

PubMed, WOS, and Scopus were systematically searched using the PRISMA protocol for relevant studies involving human subjects, including randomized clinical trials, retrospective, prospective, cohort, case reports, and case series studies. There were no restrictions on language, time, or age group. Qualified and eligible papers were used to extract data on efficacy and safety indicators, and the final relevant records were assessed for quality using the Risk of Bias in Non-Randomized Studies—of Interventions (ROBINS-I) assessment tool.

Results

12 studies with 1212 participants were included in the systematic review, with pooled data from 8 studies used for meta-analysis. No significant differences in mean differences (MDs) or odds ratio (OR) were found after the oral bicarbonate regimen, except for when urine pH fell to < 7 (MD: 0.91, 95% CI: 0.32, 1.5, P < 0.05) and the incidence of diarrhea (OR: 2.92, 95% CI: 1.69, 5.05, P < 0.05).

Conclusion

An oral bicarbonate regimen is a safe and effective way to alkalize HDMTX urine, providing a viable and cost-effective alternative to IV protocols. Further prospective multicenter studies are necessary.

Systematic review registration identifier: CRD42023379666.

Graphical abstract

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Data availability

The data supporting the findings of this study are available within the article and its supplementary material.

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Acknowledgements

Thank you to all who have contributed in various ways to the successful completion of this systematic review.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Hematology, Oncology, and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran

    Romina Kaveh-Ahangaran, Mohammad Vaezi, Amir Kasaeian & Bita Shahrami

  2. Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Abdollahi

  3. Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran

    Mohammad Abdollahi

  4. Digestive Diseases Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Amir Kasaeian

  5. Clinical Research Development Unit, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Amir Kasaeian

  6. Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Zhalleh Bahlouli, Mojtaba Mojtahedzadeh & Bita Shahrami

  7. Hematologic Malignancies Research Center, Research Institute for Oncology, Hematology, and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran

    Ghasem Janbabaei

  8. Faculty of Medicine, Semmelweis University, Budapest, Hungary

    Amirmahdi Mojtahedzadeh

  9. Development of Research and Technology Center, Deputy of Research and Technology, Ministry of Health and Medical Education, Tehran, Iran

    Shirin Djalalinia

  10. Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Shirin Djalalinia

Authors
  1. Romina Kaveh-Ahangaran
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Contributions

RK: Validation, Investigation, Writing- Original draft preparation, Writing- Reviewing and Editing, Visualization. MA: Supervision, Writing- Reviewing and Editing. MV: Conceptualization, Supervision, Writing- Reviewing and Editing, Project administration. AK: Methodology, Software, Formal analysis, Writing- Original draft preparation, Writing- Reviewing and Editing. ZB: Validation, Investigation, Writing- Reviewing and Editing. GJ: Conceptualization, Writing- Reviewing and Editing. AM: Writing- Reviewing and Editing. MM: Conceptualization, Writing- Reviewing and Editing. SD: Methodology, Validation, Investigation, Writing- Reviewing and Editing. BS: Conceptualization, Methodology, Validation, Writing- Original draft preparation, Writing- Reviewing and Editing, Project administration, Correspondence.

Corresponding author

Correspondence to Bita Shahrami.

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Kaveh-Ahangaran, R., Abdollahi, M., Vaezi, M. et al. Oral regimen for high dose methotrexate urine alkalinization: a systematic review and meta-analysis. DARU J Pharm Sci 32, 353–377 (2024). https://doi.org/10.1007/s40199-023-00499-3

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